{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:51:07Z","timestamp":1740145867264,"version":"3.37.3"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T00:00:00Z","timestamp":1497484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/502\/NE\/TBP\/2013"],"award-info":[{"award-number":["BT\/502\/NE\/TBP\/2013"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>We have previously reported that the hypericin treatment caused spermidine starvation and death of <jats:italic>Leishmania<\/jats:italic> parasite. Here, we report different molecular events under spermidine starvation and potential role of spermidine in processes other than redox homeostasis of the parasite. We have analyzed changes in expression of several genes by using quantitative gene expression analysis. Further, these changes at molecular level were also confirmed by using biochemical and cellular studies. Altered expression of several genes involved in redox metabolism, hypusine modification of <jats:styled-content style=\"fixed-case\">eIF<\/jats:styled-content>5A, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair pathway and autophagy was observed. There was decrease in Sir2<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> expression after hypericin treatment and this decrease has been found to be associated with induced <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> due to hypericin treatment as it has been rescued by either trypanothione or spermidine supplementation. Translation initiation in the parasite was decreased upon spermidine starvation. We also observed increased <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> expression upon hypericin treatment. The increase in intracellular <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NAD<\/jats:styled-content><jats:sup>+<\/jats:sup> levels as well as decrease in Sir2<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> expression of the parasite are cytoprotective mechanism towards generated <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> due to hypericin treatment possibly by inducing autophagy as indicated by increase in autophagy related gene expression and acridine orange staining. However, the autophagy needs to be established using more rigorous methodologies.<\/jats:p>","DOI":"10.1111\/cbdd.13022","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T10:56:39Z","timestamp":1494932199000},"page":"962-971","source":"Crossref","is-referenced-by-count":11,"title":["Molecular events leading to death of <i>Leishmania donovani<\/i> under spermidine starvation after hypericin treatment"],"prefix":"10.1111","volume":"90","author":[{"given":"Shalini","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati  Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekta","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati  Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchika","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati  Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati  Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4281-2504","authenticated-orcid":false,"given":"Vikash Kumar","family":"Dubey","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Guwahati  Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-009-8764-z"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2003.09.008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67629-5"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04169-14"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)34042-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.6.3105"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710970105"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033138"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.1.10600"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2013.08.014"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0320"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12449"},{"key":"e_1_2_7_14_1","first-page":"79","volume":"1982","author":"Seglen P. 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